gamma-linolenic-acid and Cell-Transformation--Neoplastic

This study examined the effects of linoleic acid (LA) and gamma-linolenic acid (GLA) on BL6 melanoma growth in cell culture and of safflower oil (SFO) which contains LA and evening primrose oil (EPO) which contains GLA, on melanoma growth when grown in mice. The delta-6-desaturase activity of the melanoma cells in the two systems was also examined and an attempt made to relate the activity of the enzyme to the effects of GLA on cell and tumour growth. LA and GLA were found to be equipotent in inhibiting growth of the in vitro cultured BL6 cells which were found to contain an appreciable level of delta-6-desaturase activity. EPO was however found to be a more potent promoter of in vivo melanoma growth in mice than SFO. Melanomas grown in mice were found to lack delta-6-desaturase activity suggesting that the EPO diet, by providing GLA, was able to compensate for the loss of enzyme activity in the melanomas. The possibility that melanomas in mice have a requirement for GLA for growth while in in vitro cultured cells excess GLA inhibits the growth of the cells through an increase in lipid peroxidation is discussed.

Topics: Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Fatty Acid Desaturases; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Linoleic Acids; Linolenic Acids; Linoleoyl-CoA Desaturase; Lipid Peroxidation; Melanoma; Mice; Mice, Inbred C57BL; Microsomes, Liver; Oenothera biennis; Plant Oils; Safflower Oil; Tumor Cells, Cultured

A number of fatty acids have been shown to inhibit the growth of malignant cells in vitro. In particular, gamma-linolenic acid (GLA) has been proposed to act as a precursor for the production of prostanoids especially prostaglandin E1 (PGE1). To test this hypothesis, the effects of GLA on cultured human breast carcinoma cells were compared with those of dihomo-gamma-linolenic acid (DGLA) the metabolite of GLA and the immediate precursor of PGE1. The influence of ethanol (which has been shown to enhance conversion of DGLA to PGE1) on the actions of each of the fatty acids was also investigated. In contrast to the inhibitory effects observed with all concentrations of GLA cell growth was promoted by the presence of 50 micrograms DGLA. Ethanol reduced the action of both GLA and DGLA possibly due to some physicochemical reaction between the alcohol and the fatty acids. The fact that the actions of GLA were not mimicked by DGLA which is the next step towards PG production casts doubt upon the role of PGE1 as mediator of the effects which have been observed with GLA in malignant cells.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Animals; Breast Neoplasms; Cell Transformation, Neoplastic; Cells, Cultured; Cytoplasmic Granules; Drug Combinations; Ethanol; Fatty Acids, Unsaturated; Female; gamma-Linolenic Acid; Growth Inhibitors; Growth Substances; Humans; Linolenic Acids; Male; Mice